Previous studies have demonstrated that 1-6% of implanted medical devices become infected, 1 and account for ~45% of nosocomial infections 2. In ventral hernia repair, infections occur in 2-10 % of the time (i.e. open surgery 7-18% and laparoscopic 0-2% infection rates) 3. Hernia repairs are among the most commonly performed operations by general surgeons throughout the world with over 1 million abdominal wall repairs performed each year in the U.S. Of these, 770,000 are inguinal repairs 4-6. Given the epidemiologic significance of inguinal and ventral hernias, determining an appropriate and effective means of hernia repair is very important. The existing evidence strongly supports routine use of prosthetic reinforcement (meshes) for the repair of hernias in most patients. Three of the major dilemmas associated with prosthetic meshes are 1) their propensity to induce chronic inflammation and excessive fibrosis, with resulting loss of mesh pliability and increased stiffness at the site of the implantation, 2) post mesh implantation infections, and 3) degradation of the mesh material in the case of polyester. In the present application we propose to develop a new class of composite surgical meshes based on a PET mesh substrate with intercalating silicone elastomer coatings that may be formulated to include one or more active pharmaceutical agents in order to: 1) enhance mesh biocompatibility and bio- stability, 2) guide tissue repair, and 3) decrease the susceptibility of the device to bacterial colonization, biofilm formation and infection. Specifically we propose to the following aims: Aim 1. Formulate a drug-free composite mesh comprising a PET substrate and a UV-curing silicone encapsulating coating, optimize the composite fabrication parameters by iteratively improving coating uniformity and integrity, and evaluate the in vivo performance of the optimized composite in a subcutaneous implant model. Aim 2. Fabricate two composite mesh configurations comprising two individual active pharmaceutical ingredient antimicrobial agents and two composite mesh configurations each comprising a binary antimicrobial agent system and characterize in vitro performance (bacteriology, drug delivery, biocompatibility index etc.) vs. dose, and choose the two optimal dose/concentration configurations for a detailed in vivo evaluation in Aim 3. Aim 3. Evaluate the in vivo performance of the top two in vitro performing novel composite surgical meshes developed in Aim 2. As a result of this proposed research we will have developed a new class of composite surgical meshes based on a polyester mesh substrate with intercalating silicone elastomer coatings that may be formulated to include one or more APIs in order to: 1) enhance mesh biocompatibility and bio-stability of the mesh, 2) decrease inflammation and fibrosis, and/or 3) decrease the susceptibility of the device to bacterial colonization, biofilm formation and infection. PUBLIC HEALTH RELEVANCE: Hernia repair is among the most commonly performed operations and routinely prosthetic reinforcement (meshes) is utilized for the repair of hernias. Major dilemmas associated with meshes are their propensity to induce inflammation; fibrosis, post mesh implantation infection and degradation of the polyester mesh material. The goal of this proposal is to develop a new class of composite surgical meshes, which are formulated to enhance biocompatibility and bio stability, decrease inflammation and decrease susceptibility to bacterial colonization and biofilm formation.